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Domschke, K.* ; Akhrif, A.* ; Romanos, M.* ; Bajer, C.* ; Mainusch, M.* ; Winkelmann, J. ; Zimmer, C.* ; Neufang, S.*

Neuropeptide S receptor gene variation differentially modulates fronto-limbic effective connectivity in childhood and adolescence.

Cereb. Cortex 27, 554-566 (2015)

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Open Access Green as soon as Postprint is submitted to ZB.

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The neuropeptide S (NPS) system contributes to the pathogenesis of anxiety. The more active T allele of the functional rs324981 variant in the neuropeptide S receptor gene (NPSR1) is associated with panic disorder (PD) and distorted cortico-limbic activity during emotion processing in healthy adults and PD patients. This study investigated the influence of NPSR1 genotype on fronto-limbic effective connectivity within the developing brain. Sixty healthy subjects (8-21 years) were examined using an emotional go-nogo task and fMRI. Fronto-limbic connectivity was determined using Dynamic Causal Modeling. In A allele carriers, connectivity between the right middle frontal gyrus (MFG) and the right amygdala was higher in older (≥14 years) than that in younger (<14 years) probands, whereas TT homozygotes ≥14 years showed a reduction of fronto-limbic connectivity between the MFG and both the amygdala and the insula. Fronto-limbic connectivity varied between NPSR1 genotypes in the developing brain suggesting a risk-increasing effect of the NPSR1T allele for anxiety-related traits via impaired top-down control of limbic structures emerging during adolescence. Provided robust replication in longitudinal studies, these findings may constitute valuable biomarkers for early targeted prevention of anxiety disorders.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Dcm ; Nps ; Npsr1 ; Anxiety ; Dynamic Causal Modeling; Social Anxiety Disorder; Functional Connectivity; Emotion Regulation; Panic Disorder; Generalized Anxiety; Facial Expressions; Pubertal Changes; Neural Activity; Amygdala; Cortex

ISSN (print) / ISBN 1047-3211

e-ISSN 1460-2199

Journal Cerebral Cortex

Quellenangaben Volume: 27, Issue: 1, Pages: 554-566

Publisher Oxford University Press

Publishing Place Cary

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Neurogenomics (ING)